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Here, we apply Similarity Network Fusion (SNF) to cluster AMD patients into putative metabolomics-derived endotypes. Using a discovery cohort of 163 AMD patients from Boston, US, and a validation cohort of 214 patients from Coimbra, Portugal, we identified four distinct metabolomics-derived endotypes with varying retinal structural and functional characteristics, confirmed across both cohorts. Patients clustered into Endotype 1 exhibited a milder form of AMD and were characterized by low levels of amino acids in specific metabolic pathways. Meanwhile, patients clustered into both Endotype 3 and 4 were associated with more severe AMD and exhibited low levels of fatty acid metabolites and elevated levels of sphingomyelins and fatty acid metabolites, respectively. These preliminary findings indicate that metabolomics-derived endotyping may offer a refined strategy for categorizing AMD patients based on their specific pathophysiological underpinnings, rather than relying solely on traditional observational clinical indicators.<\/jats:p>","DOI":"10.1038\/s41598-024-59045-z","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T19:01:43Z","timestamp":1716836503000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolomic-derived endotypes of age-related macular degeneration (AMD): a step towards identification of disease subgroups"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8832-2607","authenticated-orcid":false,"given":"Kevin","family":"Mendez","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8136-4724","authenticated-orcid":false,"given":"Ines","family":"Lains","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-1822","authenticated-orcid":false,"given":"Rachel S.","family":"Kelly","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5953-8249","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Gil","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-0833","authenticated-orcid":false,"given":"Rufino","family":"Silva","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0109-9738","authenticated-orcid":false,"given":"John","family":"Miller","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8622-6478","authenticated-orcid":false,"given":"Demetrios G.","family":"Vavvas","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0310-6129","authenticated-orcid":false,"given":"Ivana","family":"Kim","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-3996","authenticated-orcid":false,"given":"Joan","family":"Miller","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8261-3174","authenticated-orcid":false,"given":"Liming","family":"Liang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-4705","authenticated-orcid":false,"given":"Jessica A.","family":"Lasky-Su","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8494-0950","authenticated-orcid":false,"given":"Deeba","family":"Husain","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"59045_CR1","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","volume":"2","author":"WL Wong","year":"2014","unstructured":"Wong, W. 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